Method and apparatus for dispensing a liquid into a series of wells

ABSTRACT

A method for dispensing a volume of fluids from a reservoir, through a fluid outlet in fluid communication with said reservoir, into each well of at least a series of wells, whereby the fluid is dispensed into said series of wells at a continuous uninterrupted flow. A micro titer plate constructed from a hydrophobic and more in particular from a plastic material containing a plurality of series of wells and to an apparatus able to perform the above method.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is the national stage of Application No.PCT/EP01/02808, filed Mar. 8, 2001 which application claims priorityfrom EP 00200813.4, filed Mar. 8, 2000, incorporated herein byreference.

The present invention relates to a method and apparatus for dispensing apredetermined volume of fluid from a reservoir, through a fluid outletin fluid communication with said reservoir, onto a support and more inparticular into each well of at least one series of wells.

The invention is also related to a support and more in particular to amicro titer plate in which the wells are filled using the method and/orthe apparatus of the invention.

In a first aspect the invention is related to a method for dispensing apredetermined volume of a fluid, such as a chemical or biologicalreagent or any other fluid, from a reservoir, through a fluid outlet influid communication with said reservoir, into each well of at least oneseries of wells, such that the volume in each of said well issubstantially equal, whereby the method comprises a dispensing mode anda non-dispensing mode.

The invention is of particular use for providing a dispensing techniquefor high throughput screening (HTS) purposes. In general HTS can bedefined as the use of miniaturized, robotics-based technology to screenlarge compound libraries against an isolated target protein, cell ortissue in order to identify compounds that may be potential new drugs.High-throughput screening commonly depends on the development of aquantitative, pharmacologically relevant assay for the identifiedtarget, which can then be reproduced across a large number of sampleswith the use of specific supports. Series of wells are usually comprisedin multi-well or so-called micro titer plates. Such multi-well platesare currently used with a number of different applications, such as thescreening of compounds in drug discovery programs, performing cell-basedassays, performing synthesis reactions in combinatorial chemistry,performing polymerase chain reactions, etc.

Typically, high-throughput screening supports have relied on 96-wellplates as the standard, although higher-density formats (384, 864, 1536,9600 etc.) are possible. In general, due to automation and robotics aplurality of wells of the standard 96 wells is used. These supports,commonly known as micro titer plates are designed for medical or otherlaboratories are conventionally constructed from a piece of plasticcontaining a plurality of wells.

Traditionally, dosing of fluids in the wells of multi-well platesrequires quantities of fluid to be taken up in one or more pipettes,such as piëzo-electric pipettes, and their release into the wells ofsaid multi-well plates. Alternatively, metered quantities of the fluidare each time pumped through a nozzle in the successive wells. Thesepipettes or nozzles need to be positioned first on top of or into thewells of the multi-well plate. Next, the fluid is ejected or droplet perdroplet dispensed. Subsequently, these pipettes or nozzles need to bepositioned above or near these wells. As a result, a major drawback ofthese methods known in the art is that they are only suited for thehandling of multi-well plates with a limited number of wells (inparticular 96-well standard micro titer plates) but not for multi-wellplates having a larger number of wells, such as, for example, 384, 864,1536, 3456, 3840 or 9600 wells. Indeed, filling such a number of wellsusing art-known methods takes too much time and is hence inefficient.

Several automated dispensing techniques for dispensing fluids are known.

U.S. Pat. No. 6,063,339, which document was published after the prioritydate of the present invention discloses a method and apparatus fordispensing droplets in various desired patterns onto a support using amethod according to the preamble of claim 1. The disclosed method issuitable for dispensing droplets being discrete separate volumes. Thedispensed fluid may contain particles such as molecules, cells,proteins, etc. elements or particles which may be damaged whenundergoing the droplet formation.

EP-A-0 937 502 discloses a method and device for handling sample platesin which a dosing equipment is provided for dispensing. This documentproposes a dispensing method in which the sample plate is moved withrespect to a number of dosing tips. A main object of the presentinvention is to provide a method and apparatus able to dispense aprecise volume in each well of a support. Movement of the supporthowever may result in inaccurate volumes remaining in each well.Furthermore the multitude of dosing tips may, due to variations inmaterial, fabrication, wear, dimensions etc., cause differences in thedispensed volumes.

Therefore, it is an object of a first aspect of the present invention toprovide a new method that enables the dispensing of a predetermined andaccurate volume of a fluid into each well of a series of wells at highspeed.

The method according to the invention is characterised in that in thedispensing mode the fluid is dispensed at a continuous uninterruptedflow from a moving fluid outlet into a series of wells. For adding apredetermined volume of fluid into each well said fluid outlet is movedrelatively to said series of wells so that it passes over said series ofwells and during this passing said predetermined volume of fluid isdispensed into each well of said series of wells. The flow pattern ofthe fluid is a continuous uninterrupted flow, which increases thebioviability of the dispensed fluid in contrast to droplets dispension.

According to a preferred embodiment the movement of the fluid outletrelatively to said series of wells has a constant relative speed withrespect to the series of wells when passing over said series of wells. Amain object is to provide an very accurate dispensing method wherein thesame volume is dispensed in each well of the support. Due to thecombination of a continuous uninterrupted flow pattern and a constantrelative speed of the flow outlet a same volume is obtained into eachwell of a series of wells.

According to the invention it has been found that the speed at which thewells of a multi-well plate can be filled is limited by the mechanicalmovement of the fluid outlet over the series of wells. In the prior artmethods, this movement is indeed to be stopped each time when passingover one well. In the method according to the first aspect of thepresent invention, the fluid outlet is passed in a continuous movementover the series of wells. The velocity at which the outlet may pass overthe series of wells is therefore no longer limited by the limitationsimposed by a discontinuous movement of the fluid outlet.

The present invention has found that the required quantities of fluidcan be obtained in the different wells without interrupting the flow offluid out of the fluid outlet. An advantage of this preferred embodimentis clearly that a less complicated dispensing system is required sincethe flow of fluid has no longer to be interrupted at a rather highfrequency and since no control system is required to synchronise theinterruptions of the fluid flow with the movement over the series ofwells.

As elucidated above it has moreover been found that dispensing verysmall amounts of fluid in the different wells by pulsed flow of thisfluid may have deteriorative effects on the fluid, in particular whenthis fluid contains biological material such as living cells ororganisms or macro-molecules.

The present invention offers a solution to this problem which consistsin that for adding said predetermined volume of fluid into each well ofsaid series of wells, said fluid outlet is moved relatively to saidseries of wells so that it passes over said series of wells and duringthis passing an uninterrupted flow of said fluid is dispensed out of thefluid outlet.

As set forth above, the required quantities of fluid can indeed also beobtained in the different wells without interrupting the flow of fluidout of the fluid outlet. In this way, there is a smaller risk ofdamaging biological or other sensitive material which may be containedin the fluid. Although preference is given also in this aspect of theinvention to a continuous movement of the fluid outlet relative to theseries of wells, one could possibly stop the movement of the outletabove each well, in particular when the fluid is dispensed at a smallflow rate and a relatively large volume of fluid is to be added intoeach well.

In a preferred embodiment of the method according to both aspects of theinvention, the fluid is dispensed uninterruptedly at a substantiallyconstant flow rate out of said outlet moved into a straight line when itpasses over said series of wells. Preferably, the fluid outlet is movedat a substantially constant speed relative to the series of wells whenit passes over the wells. In this way a constant volume of fluid isachieved in each well.

Another aspect of the present invention is the particular use of anon-dispensing mode. Said non-dispensing mode is preferably used whenpassing from a first series to a second series of wells. As should beunderstood a series of wells is an aligned set of wells consistingessentially of one row or one column of wells. A support essentiallyconsists of a number of straight lined columns or rows being aligned inparallel to each other. In order to fill all the wells of a support thefluid outlet should be moved from a position at the end of a firstfilled series to a position at the beginning of another series to befilled.

The present invention found that an inaccurate speed pattern can arisewhen the fluid outlet is moved in bends or curved lines. A movement ofthe fluid outlet into straight lines is therefore preferred in thedispensing mode. In order to be able to obtain a constant relative speedof the fluid outlet in the straight dispensing mode, said outlet isclosed when a movement in a bend or curved line needs to be made. Amovement in a bend or curved line is always a necessity when turningfrom a first filled series to a further to be filled series. Thismovement is made in the non-dispensing mode.

Further advantages of the dispensing and the non-dispensing mode areincluded in the sub-claims.

In a second aspect the invention is related to a support, in particularto a micro titer plate constructed preferably from a hydrophobic, andmore in particular from a plastic material containing a plurality ofparallel extending series of wells forming an array of wells, wherebythe number of wells can for example be 96 organized as an array oftwelve series of eight wells or any other number of wells such as 384,864, 1536, 9600 containing a fluid dispensed in said wells by using themethod according to the present invention.

As will be further analyzed hereunder the present method provides for avery accurate dispensing method whereby substantially the same volume isdispensed into each well of the support. The average difference involume of the dispensed fluid into each well is minimal and is less than10%, preferably about 5% or less, more preferably about 4% or less andmost preferably about 3% or less.

In a third aspect the invention is also related to an apparatus fordispensing a volume of fluid from a reservoir, through a fluid outlet influid communication with said reservoir comprising:

-   -   a fluid outlet having an inlet and an outlet end for dispensing        an uninterrupted flow of fluid originating from said reservoir        onto a support comprising a series of wells, said support and/or        a fluid outlet being secured in association with a table or        carrier able to provide a relative X, X-Y or X-Y-Z motion        between the support and the fluid outlet, and    -   pumping means for providing an uninterrupted flow of fluid        through the fluid outlet from the reservoir and a controller        adapted to provide a dispensing and a non-dispensing mode,        whereby the controller further is able to control the dispensing        such that a substantial equal volume of fluid to be dispensed        into each well during a dispensing mode is provided.

Other particularities and advantages of the invention will becomeapparent from the following description of some particular embodimentsof the present method for adding predetermined quantities of fluid intoat least one series of wells. The reference numerals used in thisdescription relate to the annexed drawings wherein:

FIG. 1 shows a perspective view of a standard 1536 well plate;

FIG. 2 shows a pattern that may be followed by the liquid outlet to fillthe 1536 well plate of FIG. 1;

FIG. 3 shows an alternative pattern which may be followed to fill the1536 well plate when use is made of two liquid outlets in a fixedposition with respect to one another;

FIG. 4 shows schematically a perspective view of an apparatus that canbe used for introducing the fluid in the wells of a multi-well plate,

FIG. 5 shows schematically an embodiment of the method performed over a96 well plate,

FIGS. 6, 7, 8 and 9 show 1536 well plates filled with the methodaccording to the invention with their respective deviation in volume ineach well.

As described above the present invention is based on the theoreticalprinciple that a constant flow of fluid dispensed via a moving fluidoutlet with a constant speed over a well plate will result in a constantvolume applied in each well. The practical use of said principlerequires the use of two modes, i.e. a first dispensing mode wherein theabove principle is used along a straight line pattern of movement and anon-dispensing mode. The latter mode is used for the non-straightmovement of the fluid outlet when passing from a first filled seriestowards a second series of wells.

The present invention relates to a new method for adding a predeterminedvolume of fluid into the wells 1 of a multi-well plate 2 or moregenerally in a series of wells 1, for example in one or more rows of amulti-well plate. The plate illustrated in FIG. 1 comprises 1536 wells(32×48) and has a standard length L of about 128 mm and a standard widthW of about 86 mm. The array of wells itself has a length L of about 109mm and a width w of about 73 mm. The area of this array is thus smallerthan 100 cm². Instead of 1536 wells, the plate of these standarddimensions may contain another multiplicity of the standard 96 wellssuch as, for example, 384, 864, 3456, 3840, 6144 or 9600 wells.

The invention is not limited to the nature of the fluid to be added intothe wells. This fluid may for example be a liquid or a so-calledsemi-solid medium.

In case the wells are used with the intention to screen analytes, theyare first filled with said analytes for which various known techniquesmay be used. Subsequently, a fluid containing a so-called target is tobe applied into the wells to test whether there is any analyte-targetinteraction. The target may in particular be composed of cells, viruses,molecules, receptors, beads or combinations thereof. One additionaladvantage of the second aspect of the present invention when using itfor screening purposes is that there is little or no risk of harmingliving biological organisms, such as cells, while transferring saidliving organisms from the reservoir, which is in fluid communicationwith the outlet, to the wells in an uninterrupted flow.

In case synthesis reactions in combinatorial chemistry are performed inthe series of wells, the fluid to be added may contain for instance areagent in a particular solvent. The apparatus of the invention ishowever not limited to only one fluid outlet. Several fluid outlets canprovide for the simultaneous dispension of two or more fluids in asingle operation.

In an advantageous embodiment of the method according to the invention,the fluid is no longer separately added into the individual wells 1 bymeans of pipettes or by means of a pump which pumps each time a metereddose in the wells. Instead, the fluid is introduced in a series of wells1 in a dispensing mode by dispensing an uninterrupted flow of the fluidout of a fluid outlet 3 and by simultaneously passing this fluid outlet3, in a continuous straight lined movement with a constant speed overthe series of wells 1. Obviously, when having passed over the series ofwells 1, the fluid flow may be interrupted. It has been found thatnotwithstanding the fact that the movement of fluid outlet 3 is notstopped above each of the wells and the fluid flow is not interruptedwhen moving to a next well, this method still allows to achieve therequired quantities of fluid in each of the wells. Compared to existingdiscontinuous dosing techniques, this method offers the advantage that alarger amount of wells can be filled with the required precise volume ofliquid in a much shorter period of time.

Before describing the further particularities of the method according tothe invention, a short description will now be given of an apparatusthat is suitable for performing this method.

The apparatus illustrated in FIG. 4 comprises a frame 4 supported byfour legs 5. On top of the frame 4, two reservoirs 6, 7 are providedeach containing a fluid to be introduced in the wells 1 of a multi-wellplate. The reservoirs 6, 7 are connected on the one hand to a source ofpressurized gas 8 and on the other hand, through flexible tubes 9, 10 totwo fluid outlets consisting of the dispense needles 11, 12. Thesedispense needles 11, 12 comprise a valve, for example a so-calleddiaphragm valve or a piëzo-electric valve, for controlling the flow offluid through the needles. As valve, use can for example be made of the750 V series of general purpose diaphragm valves of EFD. The bottom ofthese valves is provided with a tip adapter onto which tips 13, 14 ofdifferent sizes and showing in particular a different outlet 3, can bemounted. For controlling the operation of the dispense needles 11, 12,these needles are connected to a valve controller through theintermediary of pneumatic tubings 15, 16. Since the valve controller andthe dispense needles are known per se, no further description will begiven thereof.

In the apparatus illustrated in FIG. 4, the needles 11, 12 are mountedon a carriage 17 which is movable up and downwards, according to doublearrow 18 (Z-direction) on a guiding support 19 by means of an electricmotor 20. The multi-well plate which is to be filled with the liquid isto be inserted in a plate holder 21 situated underneath the needles 11,12 and showing a recess 22 with dimensions adapted to the outerdimensions of the standard multi-well plates 2. The plate holder 21 isslideably mounted on a carriage 23 so that it can be moved, according toa reciprocating movement, in the direction of double arrow 24(X-direction) on the carriage 23 by means of an electric motor 25 whichis also mounted on this carriage 23. In order to be able to move theplate holder 21 in two dimensions, the carriage 23 is slideably mounted,in the direction of double arrow 26 (Y-direction), onto a guidingsupport 27. This guiding support 27 is mounted within the frame and isprovided with an electric motor 28 for moving the carriage 23, and hencethe plate holder 21, in the Y-direction.

The apparatus shown in FIG. 4 comprises a programmable control unit forcontrolling the operation of the valve controller and the operation ofthe motors 20, 25 and 28, i.e. the movements of the dispense needles 11,12 in the Z-direction and the movements of the plate holder 21 in the X-and Y-direction. The control unit is further adapted to provide adispensing and a non-dispensing mode. Further details of the controlunit and the construction of the apparatus in general will not be givensince a person skilled in the art will readily be able to construct suchan apparatus and since many modifications can be applied to theillustrated apparatus without departing from the scope of the presentinvention. If necessary a cover (not shown) can be provided for securingthe dispensing area.

Turning now back to the method according to the preferred embodiment ofthe invention wherein a series of wells 1 of a multi-well plate 2 isfilled with fluid from a reservoir 6 or 7 by passing the fluid outlet 3of the needles 13 or 14 in a continuous movement over this series ofwells 1 while dispensing an uninterrupted flow of fluid out of theoutlet, it will be clear that only a relative movement of the outlet 3with respect of the multi-well plate 2 is required and that in otherwords either the outlet 3 and/or, as in the apparatus illustrated inFIG. 4, the plate 2 are moved.

For adding the fluid into the wells 1 of the plate 2 illustrated in FIG.1, the different wells thereof could be considered as one series ofwells which can be filled by one continuous movement of the outlet overthe multi-well plate according to a pattern going from one well to theother and covering the entire surface of this plate. In this case, themovement direction of the outlet has however to be changed above certainwells so that very sudden changes of direction are required in order toavoid that the “corner” wells receive too much fluid (unless for examplethe wells on two opposite sides of the well may contain more fluid orunless the flow of fluid is interrupted when passing from one well toanother).

In a preferred embodiment of the invention, the array of wells 1 of themulti-well plate 2 is therefore divided in several substantiallyparallel series of wells, in particular rows or columns, extending fromone side of the array to the other. In that case a pattern asillustrated in FIG. 2 can be followed. According to this pattern, whenhaving passed over one row, the fluid outlet 3 turns in an area outsidethe array of wells 1 to another row of wells. In this way, the volume offluid introduced in the wells at both opposite ends of the plate iseasier to control. Moreover, a less sharp turning has to be made whenreturning not in the next row but as illustrated in FIG. 2, by skippinga number of rows and by filling these rows during the next turns.

FIG. 5 provides for another embodiment of the method over a 96 wellplate in which the dispensing mode is indicated in the bold straightlines and the interrupted curved lines indicate the non-dispensing mode.Preferably bend section of the curved motion is performed outside thearea of the support, such that no risk for dispensing a loose dropletcan occur. More preferably a straight lined motion as an extension ofthe turn or bend is provided in the non dispensing mode such that whenagain the mode is switched to the dispensing mode a constant speed isalready available for the fluid outlet.

When passing over the area outside the array of wells, the flow of fluidout of the fluid outlet is preferably interrupted. Before passing over anext series of wells, the flow of fluid is started again, preferablysomewhat in advance so as to fill the first well of each series at therequired flow rate.

As described here-above, the apparatus illustrated in FIG. 4 comprisestwo dispense needles 11 and 12 with a fluid outlet 3 and two fluidreservoirs 6, 7. These reservoirs 6, 7 may be filled with the same orwith different fluids. When filled with the same fluid, it is of coursepossible to connect both outlets 3 to one and the same reservoir.

Both fluid outlets are fixed in the carriage 17 on a fixed distance fromeach other. This distance may correspond for example to half the numberof rows of the multi-well plate. In this way, the plate can be filledaccording to a pattern as illustrated in FIG. 3, whereby each outletfollows, on one half of the plate, a pattern similar to the patternillustrated in FIG. 2. It will be clear that with more outlets, similarpatterns can be followed.

In a preferred embodiment, when the outlet 3 passes over one of saidseries of wells 1, the fluid is dispensed at a substantially constantflow rate out of the outlet. When the fluid outlet moves at asubstantially constant speed with respect to the multi-well plate whenit passes over this series of wells, a substantially constant volume offluid is dispensed in the different wells of this series.

If desired, the speed of the outlet with respect to the multi-well platecan either continuously or discontinuously be increased or decreasedwhen passing over a series of wells. In this way, the volume of fluidintroduced in the wells will increase or decrease accordingly.

The flow rate at which the fluid is dispensed out of the outlet may forexample be comprised between 0.001 and 2000 μl/sec and preferablybetween 10 and 1000 μl/sec and more preferably between 200 and 500μl/sec. The volume of fluid which may be added into each well may varywithin wide ranges, in particular between 0.00025 and 100 μl. In casethe flow rate comprises for example 350 μl/sec, one row of a 1536 wellplate (32×48 wells) would for example be filled with 7 μl per well inabout 1 sec. Filling the entire plate would take then about half aminute. Filling a row of a plate with a larger number of wells mayrequire substantially the same time since each of the wells has normallyto be filled with less fluid. Filling a 3456 well plate (48×72 wells)would take then about 50 sec, or even less in case two or more dispenseoutlets are used.

The above flow rates enable the use of very narrow needle tips or outletopenings. The outlets may have for example an inner diameter of between40 and 500 μm, and more particularly of between 50 and 200 μm, at leastin case the fluid has a viscosity comparable to the viscosity of water.It will be clear that such narrow jets of fluid will enable to fillmulti-well plates having even up to 9600 wells (80×120 wells) on thestandard area of about 109×73 mm. In this way, even multi-well plateshaving such an extremely high number of wells could be filled with fluidin an acceptable period of time by employing the method according to theinvention.

In the method according to a further aspect of the invention, therelatively narrow flow of fluid dispensed out of the outlet is partiallydeposited onto the top surfaces of the walls separating the wells. Ithas been found that this volume of fluid is however substantiallyequally divided over two successive wells when these wells are adjacentto one another. Preferably, the top surface of the partition wallsbetween the wells is repellent for the fluid which is to be introducedtherein so that small droplets are formed which roll off this surface sothat no fluid remains on top thereof. Making this top surface somewhatconvex, pointed or inclined can of course enhance this phenomenon. Inthe area where the fluid outlet or in other words the flow of fluidpasses, the top surfaces of the partition walls between the wells havepreferably a width smaller than 1 mm, and in particular smaller than 0.6mm. Depending on the surface tension of the fluid and the adherencebetween the fluid and the surface of the partition walls, substantiallyno fluid will remain on top of such walls, even if these walls have noconvex but a flat top surface. The constant speed of the fluid outletrelative to the series of wells in the dispensing mode is in generalsmaller than 300 mm/sec and preferably about 150 mm/sec.

From the above description, it will be clear that many modifications canbe applied to the described embodiments without leaving the scope of theannexed claims.

It is for example possible to provide a fluid reservoir in the dispenseneedles 11, 12 themselves so that the tubings 9 and 10 can be omitted.Further, instead of moving the dispense needles 11, 12, it is alsopossible to move the plate holder 21 or to move the dispense needles 11,12 in one direction and the plate holder 21 in another direction.

The plate holder 21 may also be arranged to carry two or more multi-wellplates. In this case, the dispense needles are preferably arranged onsuch a mutual distance that they move each simultaneously above one ofthe multi-well plates.

Finally, instead of using valves in the dispense needles and apressurized source of fluid, a pump could be provided in the tubingsleading from the reservoirs 7, 8 to the dispense needles.

FIGS. 6, 7, 8 and 9 show four examples of filled 1536 well plates usingthe method of the invention. A rhodamine suspension is dispensed inthese 1536 wells in a intermittent pattern of dispensing mode over thewell in a straight line with a constant speed and a non-dispensing modewhen moving from the filled series to a series to be filled. The plateswere scanned and the pixel values calculated. The deviation wascorrelated to a deviation in volume and depicted into each well. Asclearly visualized a very small deviation is obtained. In order tofurther improve the dispensing method a specific control program isdesigned. A main characteristic of said control is that the dispensingvalve has a certain reaction time which becomes clear in the fact thatthe first and the last well of a series have a rather higher deviation.When taken the latter into account by providing a lead-in and a lead-outrespectively at the beginning and at the end of the dispensing modelower deviation is obtained.

1. Method for dispensing a predetermined volume of a fluid from areservoir, through a fluid outlet in fluid communication with saidreservoir, into each well of at least one series of wells, such that thevolume in each of said well is substantially equal, whereby the methodcomprises a dispensing mode and a non-dispensing mode, whereby thedispensing mode is characterized in that, the fluid is dispensed at acontinuous uninterrupted flow from a moving fluid outlet into saidseries of wells.
 2. Method according to claim 1, wherein the dispensingmode is further characterized in a movement of the fluid outletrelatively to said series of wells at a constant relative speed withrespect to the series of wells when passing over said series of wells.3. Method according to claim 1, wherein the fluid outlet is moved alonga straight line over the series of wells, whereby said series of wellsconsist essentially of wells arranged in a straight line.
 4. Methodaccording to claim 1, wherein the non-dispensing mode is characterizedin that no fluid is being dispensed.
 5. Method according to claim 4,wherein the non-dispensing mode is further characterized by the movementof the fluid outlet from a first series of wells to a second series ofwells in curved and/or straight lines whereby said series of wellsconsists essentially of wells arranged in a straight line preferablyparallel to each other.
 6. Method according to claim 5, wherein thecurved and/or straight lines form a bend from a first series of wells toa second series of wells.
 7. Method according to claim 6, whereby thebend is a bend over 180°, preferably having a straight lined extensionat the end of the bend.
 8. Method according to claim 7, whereby the bendis a circular bend.
 9. Method according to claim 1, characterized inthat the fluid is dispensed at a flow rate of between 0.001 and 2000μl/sec and preferably at a flow rate of between 10 and 1000:1/sec andmore preferably between 200 and 500 μl/sec.
 10. Method according toclaim 1, characterized in that the continuous speed of said fluid outletis smaller than 300 mm/sec and preferably around 150 mm/sec.
 11. Methodaccording to claim 1, characterized in that said predetermined dispensedvolume per well in a series of wells is between 0.00025 and 100 μl. 12.Method according to claim 1, characterized in that said series of wellsis included in a support of several series of wells, extending parallelfrom one side of the support to the other, whereby said series of wellsare being filled in the dispensing mode with a predetermined volume offluid by passing said outlet over said support.
 13. Method according toclaim 12, whereby after having added said predetermined volume of fluidinto each well of one of a first series of wells, said fluid outlet ismoved with respect to the support in a non-dispensing mode in an areaoutside said support to pass to a second series of wells.
 14. Methodaccording to claim 1, in which the average difference in volume of thedispensed fluid into each well is less than 10%, preferably about 5% orless, more preferably about 4% or less and most preferably about 3% orless.
 15. Micro titer plate constructed from a hydrophobic and more inparticular from a plastic material containing a plurality of parallelextending series of wells forming an array of wells, whereby the numberof wells can for example be 96 organized as an array of twelve series ofeight wells or any other number of wells such as 384, 864, 1536, 9600containing a fluid dispensed in said wells by using the method accordingto claim
 1. 16. Micro titer plate according to claim 15, wherein theaverage deviation in volume of the wells is less than 10%, preferablyabout 5% or less, more preferably about 4% or less and most preferablyabout 3% or less.
 17. Apparatus for dispensing a volume of fluid from areservoir, through a fluid outlet in fluid communication with saidreservoir comprising: a fluid outlet having an inlet and an outlet endfor dispensing an uninterrupted flow of fluid originating from saidreservoir onto a support comprising a series of wells, said supportand/or a fluid outlet being secured in association with a table orcarrier able to provide a relative X, X-Y or X-Y-Z motion between thesupport and the fluid outlet, and pumping means for providing anuninterrupted flow of fluid through the fluid outlet from the reservoirand a controller adapted to provide a dispensing and a non-dispensingmode, whereby the controller further is able to provide a substantialequal volume of fluid to be dispensed into each well during a dispensingmode.
 18. Apparatus according to claim 17 whereby the fluid outletcomprises a valve adapted to be closed when a dispensing mode is beingfollowed by a non-dispensing mode or to be opened when a non-dispensingmode is followed by a dispensing mode.
 19. Apparatus according to claim17, whereby the dimension of the apparatus is such that a cover isprovided for securing the dispensing area.